{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T19:44:59Z","timestamp":1775504699716,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively.<\/jats:p>","DOI":"10.3390\/molecules28031007","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:06:14Z","timestamp":1674104774000},"page":"1007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide"],"prefix":"10.3390","volume":"28","author":[{"given":"Zhonghao","family":"Qiu","sequence":"first","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China"},{"name":"School of Chemistry Engineering, Sichuan University of Science & Engineering, Zigong 643000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiandong","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongxu","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zirui","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyong","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Chemistry Engineering, Sichuan University of Science & Engineering, Zigong 643000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanhua","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ejphar.2010.09.019","article-title":"Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit","volume":"649","author":"Busby","year":"2010","journal-title":"Eur. 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